See instructions): The primary objective of this Pharmacological Sciences Training Grant is to develop scientists, equipped with the necessary background in the biological and chemical sciences and training in the application of modern tools of research and instrumental techniques, to undertake and direct fundamental research related to drug action, metabolism and kinetics. Trainees follow tracks that emphasize training in four broadly defined areas: (I) drug metabolism, (II) pharmacokinetics, drug transport and delivery, (III) cellular and molecular pharmacology and (IV) structure and drug design, that presently exist in the departments of Medicinal Chemistry, Pharmaceutics and Pharmacology. Didactic components involve individualized, highly multidisciplinary programs of coursework and seminars which center around the biological and chemical sciences. Researchcomponents of the program emphasize training in mechanistic and bioanalytical aspects of drug metabolism and toxicology, pharmacokinetics and pharmacodynamics, drug transporter function and regulation, pharmacogenetics, mechanisms and regulation of cell signaling, neuropharmacology and X-ray, NMR and proteomic approaches to structure elucidation of protein-ligand interactions of pharmacological interest. In this competitive renewal of the Pharmacological Sciences National Research Service Award program, support is requested for 16 predoctoral trainees in the first year increasing to 17 and 18 trainees, in the second and fourth years, respectively. The selection of trainees will be on a competitive basis primarily among second year or more advanced graduate students who are committed to research in one of the aforementioned areas. RELEVANCE (See instructions): The training that is provided relates to how drugs used to treat human diseases and other disorders act on the body (pharmacology), and how the body acts on drugs (metabolism and pharmacokinetics). These fundamental areas of knowledge are critical to optimizing the use of drugs already on the market as well as ongoing national and international efforts to discover and develop new therapeutic agents.